Power-law properties of nocturnal arrhythmia avalanches: A novel marker for incident cardiovascular events.

BACKGROUND: Bursting nonsustained cardiac arrhythmia events are a common observation during sleep. OBJECTIVES: The purpose of this study was to investigate the hypothesis that nocturnal arrhythmia episode durations could follow a power law, whose exponent could predict long-term clinical outcomes. METHODS: We defined "nocturnal arrhythmia avalanche" (NAA) as any instance of a drop in electrocardiographic (ECG) template-matched R-R intervals ≥30% of R-R baseline, followed by a return to 90% of baseline. We studied NAA in ECG recordings obtained from the Sleep Heart Health Study (SHHS), Osteoporotic Fractures in Men Study (MrOS) Study, and Multi-Ethnic Study of Atherosclerosis (MESA). The association of nocturnal arrhythmia durations with a power-law distribution was evaluated and the association of derived power-law exponents (α) with major adverse cardiovascular (CV) events and mortality assessed with multivariable Cox regression. RESULTS: A total of 9176 participants were studied. NAA episodes distribution was consistent with power-law vs comparator distributions in all datasets studied (positive log likelihood ratio of power-law vs exponential in MESA: 83%; SHHS: 69%; MrOS: 81%; power-law vs log-normal in MESA: 95%; SHHS: 35%; MrOS: 64%). The NAA power-law exponent (α) showed a significant association of with adverse CV outcomes (association with CV mortality: SHHS hazard ratio 1.39 [1.07-1.79], P = .012; MrOS hazard ratio 1.42 [1.02-1.94], P = .039; association with CV events: MESA HR 3.46 [1.46-8.21], P = .005) in multivariable Cox regression, after adjusting for conventional CV risk factors and nocturnal ectopic rate. CONCLUSION: The NAA power-law exponent is a reproducible, predictive marker for incident CV events and mortality.

Finger pulse plethysmography predicts gestational hypertension, preeclampsia and gestational diabetes.

BACKGROUND: Pregnancy complications related to hypertension can affect both mother and newborn. Pulse wave attenuation (PWA) captured through fingertip photoplethysmography (PPG) provide valuable insights into maternal acute hemodynamic and autonomic vascular function. Here, we quantify the nocturnal dynamics of PWA during early pregnancy and assess their association with the development of gestational hypertension, preeclampsia and gestational diabetes. METHODS: PWA dynamics were assessed on overnight polysomnography-derived PPG signals from a cohort of 2714 pregnant women (mean age: 26.8 ±â€Š5.5 years) enrolled in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b). We determined the average duration (PWA duration ) and depth (PWA depth ) of PWA events in all women. RESULTS: Odds ratio (OR) analysis-adjusted common confounders indicates that an average PWA duration greater than 8.74 s was associated with the increased risk of gestational hypertension [OR = 1.75 (1.27-2.39), P  < 0.001]. Similarly, average PWA depth greater than 1.19 was associated with an increased risk of preeclampsia [OR = 1.53 (1.01-2.33), P  = 0.045] and gestational diabetes [OR = 1.66 (1.01-2.73), P  = 0.044]. CONCLUSION: PWA attenuation dynamics during early pregnancy predict the risk of developing gestational hypertension and diabetes condition for women in their later trimesters. Potentially obtainable from smart wearable consumer devices, PWA analysis offers a low-cost, accessible and scalable marker that can enhance the management of pregnancy-induced cardiometabolic issues.

A real-time signal processing software package for the electrophysiology laboratory.

BACKGROUND: Real-time signal processing has to date been difficult to implement in the clinical electrophysiology laboratory. To date, no open access software solutions are available in electrophysiology (EP) laboratories to facilitate real-time intraprocedural signal analysis. We aimed to develop an open access, scalable Python plug-in to allow real-time signal processing during human EP procedures. METHODS AND RESULTS: A Python-based plug in for the widely available EnsiteX mapping system was developed. This plug-in utilized the LiveSync feature of the system to allow real-time signal analysis. An open access library was developed to allow end-users to implement real-time signal analysis using this platform, implemented in the Python programming language https://github.com/anand9176/WaveWatch5000Public. CONCLUSION: We have developed and demonstrated the feasibility of a readily scalable and open-access Python-based plug in to an electroanatomic mapping system (EnSiteX) to allow real-time processing and display of electrogram (EGM) based information for the procedural electrophysiologist to view intraprocedurally in the electrophysiology laboratory. The availability, to the clinician, of traditional and novel EGM-based metrics at the time of intervention, such as atrial fibrillation ablation, allows for key mechanistic insights into critical unresolved questions regarding arrhythmia mechanism.

Generalised linear model of periodic limb movements.

During sleep, the lower extremities exhibit periodic repetitive movements which are referred to as Period Limb Movement (PLM). Polysomnography (PSG) is the gold standard for diagnosing periodic limb movement disorder. The frequency of PLM episodes per hour of sleep (PLMI) determines the severity of the condition. PLM are generated by a dynamic process, however PLMI measures only the average PLM rate and does not capture the dynamic properties of PLM. Here, we characterise PLM dynamics using a generalised dynamic model as a function of sleep stage, timing of past PLM events and adjacent sleep disordered-breathing events. We analysed PSG recordings of 237 men and 222 women enrolled in the Multi-ethnic Study of Atherosclerosis (MESA) dataset to model dynamic PLM features. We statistically analysed whether these dynamics are associated with sex, age, and BMI. Modelling suggests instantaneous PLM rates are greater in men than women and higher in N1 and N2 non-rapid eye movement sleep than N3 and rapid eye movement sleep. The generalised model constitutes statistically robust approach towards the characterisation of periodic limb movement.Clinical Relevance- The generalised model may enable differentiated diagnostics of periodic limb movement disorder.

Symbolic dynamics of sleep heart rate variability is associated with cognitive decline in older men.

We aimed to investigate the association between autonomic and cognitive functions in older men. We investigated heart rate variability (HRV) during sleep using time domain metrics and symbolic dynamics analysis of inter-beat intervals. These metrics were statistically analysed for associations with cognitive function which was elicited by administering the modified mini-mental state examination (3MS) and the Trail making test part-B in older men participating in the MrOS sleep study.Multivariable linear regression adjusted for age, body-mass-index (BMI), apnea-hypopnea index (AHI) and arousal index (A.I.) showed that symbolic dynamics of HRV especially the 0V% which is a measure of sympathetic outflow to the heart during rapid eye movement (REM) sleep is significantly associated with 3MS and Trail B scores. In conclusion, nonlinear HRV during sleep provides a unique window to probe the association between cognitive and autonomic function.Clinical Relevance- This study shows that cognitive decline is associated with altered cardiac autonomic function.

Percolation theory as a conceptual framework to explain spontaneous atrial fibrillation termination: a pilot study.

Atrial fibrillation (AF) strikingly possesses the ability to abruptly transition into more organized electrical activity and spontaneously terminate, even after persisting for long periods. Despite being central to the clinical behavior and treatment of AF, these phenomena remain incompletely understood. In this paper, we hypothesized that the spontaneous termination of AF may represent a type of percolation phase transition, which is more likely to occur when a domain spanning cluster of refractory sites in the atrium are connected (called a 'percolation cluster'). This was assessed in n=50 computational simulations of AF developed using the Aliev-Panfilov (APV) 2-dimensional cell model. In self-terminating simulations of AF, it was found that the average refractory cluster size, χ(p) (median: 647.7), and the largest refractory cluster size, M1 (median: 1702.3), abruptly increased just prior to AF spontaneously terminating, indicating the onset of the formation of a domain spanning percolation cluster. In contrast, simulations of sustained AF did not demonstrate an increase in χ(p) (median: 463.0) and M1 (median: 1448.2). Self-terminating AF simulations also demonstrated hallmark properties characteristic of a percolation phase transition, such as an abrupt increase in χ(p) at the critical occupation probability pc. The cluster size distribution was also shown to obey a power law for various occupation probabilities p, also indicative of a percolation phase transition. Collectively, these properties suggests that the spontaneous termination of AF could be a form of percolation phase transition, which could provide new insights for AF treatment.

Contributors to beat-to-beat stroke volume variability during acute mental stress in healthy volunteers.

Acute mental stress elicits sympathetic activation, increasing heart rate and shortening the QT interval, but it is unknown whether this activation translates to stroke volume (SV) changes. Multivariate power spectral decomposition was used to assess the influence of heart rate and QT variabilities on SV variability at rest and during acute mental stress. Acute mental stress elicits mild but statistically significant increase in SV variability. Heart rate variability contributes almost one third of SV variability, while the contribution of QT variability is below 3%. In conclusion, although heart rate variability appears to contribute directly to increase in SV variability during acute mental stress, most of SV variability is attributed to sources independent of heart rate and QT variabilities.Clinical Relevance-Acute mental stress elicits small fluctuations in stroke volume in healthy volunteers. Its significance for clinical populations remains to be established.

Nocturnal pulse wave amplitude attenuations are associated with long-term cardiovascular events.

OBJECTIVES: Photoplethysmography (PPG) is an established technology for detecting pulse rate and pulse wave irregularities. However, whether temporal variations in pulse wave amplitudes, reflecting a combination of acute hemodynamic or autonomic responses to changes in overall vascular function, carry prognostic information remains unclear. To quantify nocturnal temporal pulse wave amplitude (PWA) attenuations and evaluate its association with long-term cardiovascular (CV) events in a large, racially diverse sample of men and women. METHODS: Temporal PWA attenuations were determined based on the slopes between the upper and lower envelopes of PPGs derived from overnight polysomnography of 1957 participants (899 men, 1058 women, mean age 68.2 ± 9.1 years) of the Multi-Ethnic Study of Atherosclerosis. The nocturnal PWA attenuation index was defined as the cumulative duration of all PWA attenuation events relative to total sleep duration. RESULTS: Nocturnal PWA attenuation index was greater in men than in women by almost 13% (16.3 ± 8.9% vs. 14.4 ± 7.9%, p < 0.001). The nocturnal PWA attenuation index was highest in Chinese-American participants (17.9 ± 9.2%) and lowest in African-Americans (13.5 ± 8.1%). During a median follow-up of 4.9 years, 94 CV events occurred. In multivariable Cox proportional hazard analysis adjusted for typical confounders, the nocturnal PWA attenuation index <15.2% was associated with CV events (HR = 1.58 [1.02-2.45], p = 0.042). CONCLUSIONS: Nocturnal PWA attenuation index is inversely associated with the risk of CV events, particularly in men and African-Americans. The PPG-derived nocturnal PWA attenuation index could be simply obtained from smart wearable consumer devices and may provide a low-cost, accessible and scalable CV risk marker.

Sleep Arousal-Related Ventricular Repolarization Lability Is Associated With Cardiovascular Mortality in Older Community-Dwelling Men.

BACKGROUND: Sleep is fragmented by brief arousals, and excessive arousal burden has been linked to increased cardiovascular (CV) risk, but mechanisms are poorly understood. RESEARCH QUESTION: Do arousals trigger cardiac ventricular repolarization lability that may predispose people to long-term cardiovascular mortality? STUDY DESIGN AND METHODS: This study analyzed 407,541 arousals in the overnight polysomnograms of 2,558 older men in the Osteoporotic Fractures in Men sleep study. QT and RR intervals were measured beat-to-beat starting 15 s prior to arousal onset until 15 s past onset. Ventricular repolarization lability was quantified by using the QT variability index (QTVi). RESULTS: During 10.1 ± 2.5 years of follow-up, 1,000 men died of any cause, including 348 CV deaths. During arousals, QT and RR variability increased on average by 5 and 55 ms, respectively, resulting in a paradoxical transient decrease in QTVi from 0.07 ± 1.68 to -1.00 ± 1.68. Multivariable Cox proportional hazards analysis adjusted for age, BMI, cardiovascular and respiratory risk factors, sleep-disordered breathing and arousal, diabetes, and Parkinson disease indicated that excessive QTVi during arousal was independently associated with all-cause and CV mortality (all-cause hazard ratio, 1.20 [95% CI, 1.04-1.38; P = .012]; CV hazard ratio, 1.29 [95% CI, 1.01 -1.65; P = .043]). INTERPRETATION: Arousals affect ventricular repolarization. A disproportionate increase in QT variability during arousal is associated with an increased all-cause and CV mortality and may reflect ventricular repolarization maladaptation to the arousal stimulus. Whether arousal-related QTVi can be used for more tailored risk stratification warrants further study, including evaluating whether arousal suppression attenuates ventricular repolarization lability and reduces subsequent mortality. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT00070681; URL: www. CLINICALTRIALS: gov.

Sleep arousal burden is associated with long-term all-cause and cardiovascular mortality in 8001 community-dwelling older men and women.

AIMS: To quantify the arousal burden (AB) across large cohort studies and determine its association with long-term cardiovascular (CV) and overall mortality in men and women. METHODS AND RESULTS: We measured the AB on overnight polysomnograms of 2782 men in the Osteoporotic Fractures in Men Study (MrOS) Sleep study, 424 women in the Study of Osteoporotic Fractures (SOF) and 2221 men and 2574 women in the Sleep Heart Health Study (SHHS). During 11.2 ± 2.1 years of follow-up in MrOS, 665 men died, including 236 CV deaths. During 6.4 ± 1.6 years of follow-up in SOF, 105 women died, including 47 CV deaths. During 10.7 ± 3.1 years of follow-up in SHHS, 987 participants died, including 344 CV deaths. In women, multivariable Cox proportional hazard analysis adjusted for common confounders demonstrated that AB is associated with all-cause mortality [SOF: hazard ratio (HR) 1.58 (1.01-2.42), P = 0.038; SHHS-women: HR 1.21 (1.06-1.42), P = 0.012] and CV mortality [SOF: HR 2.17 (1.04-4.50), P = 0.037; SHHS-women: HR 1.60 (1.12-2.28), P = 0.009]. In men, the association between AB and all-cause mortality [MrOS: HR 1.11 (0.94-1.32), P = 0.261; SHHS-men: HR 1.31 (1.06-1.62), P = 0.011] and CV mortality [MrOS: HR 1.35 (1.02-1.79), P = 0.034; SHHS-men: HR 1.24 (0.86-1.79), P = 0.271] was less clear. CONCLUSIONS: Nocturnal AB is associated with long-term CV and all-cause mortality in women and to a lesser extent in men.

Sleep Arousal and Sudden Changes in Cardiac QT Interval.

Sleep arousal is generally defined as an abrupt shift in EEG frequency with a duration of 3-16 seconds. Arousal from sleep expected to cause sudden changes in the cardiovascular system that can manifest as cardiac responses. In this paper, our objective was to investigate how cardiac characteristics change due to arousal. We focused on the QT interval fluctuations in ECG during the occurrence of arousals. We analysed 7373 sleep arousals collected from 50 males that were older than 65 years. We analysed the ECG signal 5 seconds prior to and 10 seconds after each arousal onset (Pre and Post-Onset). Q and T waves were detected for all Pre and Post-Onset windows to estimate their time intervals. To find out whether the QT interval, a marker of ventricular activation, is modulated by arousal onset, we have applied graphical and statistical analysis. Our observations indicate that in 47 out of 50 subjects (94%), the average QT interval of all arousal significantly shortened at arousal onset. We observed similar outcomes for different types of arousals, indicating that the shortening in average QT interval is independent of the type of arousal. We also studied the relative QT interval change during arousal. The distribution of relative QT interval changes demonstrates that around 60% of arousals increase or decrease QT interval by a maximum of 20%. The probability of QT time interval shortening was twice that of QT interval lengthening.

Blood pressure and cardiovascular parameters during sleep arousals.

Sleep arousal is generally known as a transient episode of wakefulness into the sleepiness. Sleep arousals can be classified based on their association and accompany with pathological episodes. In this paper, our objective was to find out whether various types of sleep arousals influence on blood pressure and Heart Rate Variability (HRV). We analysed continuous Diastolic and Systolic Blood Pressures (DBP and SBP), Pulse Transit Time (PTT) as well as High and Low Frequency components (HF and LF) of HRV in different types of arousals. We developed Slope Index (SI) to determine whether a feature was ascending or descending before, during and after the occurrence of a sleep arousal. Slope Index Positive Percentage (SIPP) was created and computed for all features to find out the percentage of arousals with an ascending trend of a cardiovascular feature. In pre-arousal epochs, we obtained SIPPDBP= 48.9%, SIPPSBP = 48.2% and SIPPLF = 41%. Whilst during the arousal episodes, the SIPPDBP, SIPPSBP and SIPPLF increased to 57.2%, 57.4% and 78.9%, correspondingly. This means that during arousal occurrence these parameters were likelier to rise. Whereas SIPP of PTT and HF component of HRV during arousals were less than prearousal. This indicated PTT and HF were highly probable to drop during the arousal than to rise. The high SIPPDBP and SIPPSBP parameters, approximately 76%, during the arousals indicates that sleep arousals may cause a sudden increase in blood pressure.

Photoplethysmography derivatives and pulse transit time in overnight blood pressure monitoring.

Overnight continuous blood pressure measurement provides simultaneous monitoring of blood pressure and sleep architecture. By this means, we are able to investigate whether different sleep events are associated to blood pressure fluctuations. In this paper, we used the Pulse Transit Time (PTT) to develop and evaluate functions for measurement of blood pressure. We focused on the first and second derivatives of fingertip Photoplethysmography (PPG) recordings to detect PPG critical points. By applying R wave of ECG and PPG critical points, we created two PTT-based models for estimation of systolic and diastolic blood pressure (SBP and DBP). Seven subjects polysomnography datasets that contained PPG, ECG and blood pressure recordings were utilised to validate and compare developed PTT-BP functions. Results found that if the peak of the first derivative of PPG (VPG) was considered as the pulse pressure arrival point, the resulted PTT (PTTV) would more accurately predict both SBP and DBP. The average R-squared coefficient for SBP and DBP were correspondingly 0.593 and 0.416. The obtained mean error for PTTV based functions in SBP was ±3.96 mmHg with standard deviation of 1.41 mmHg and in DBP was ±6.88 mmHg with standard deviation of 3.03 mmHg. We concluded PTT detected from VPG is a reliable and suitable maker for overnight continuous blood pressure monitoring.

Pulse transit time and heart rate variability in sleep staging.

This paper presents a new and robust algorithm for detection of sleep stages by using the lead I of the Electrocardiography (ECG) and a fingertip Photoplethysmography (PPG) sensor, validated using multiple overnight PSG recordings consisting of 20 human subjects (9 insomniac and 11 healthy). Heart Rate Variability (HRV) and Pulse Transit Time (PTT) biomarkers which were extracted from ECG and PPG biosignals then employed to extract features. Distance Weighted k-Nearest Neighbours (DWk-NN) was used as classifier to differentiate sleep epochs. The validation of the algorithm was evaluated by Leave-One-Out-Cross-Validation method. The average accuracy of 73.4% with standard deviation of 6.4 was achieved while the algorithm could distinguish stages 2, 3 of non-rapid eye movement sleep by average sensitivity of almost 80%. The lowest mean sensitivity of 53% was for stage 1. These results demonstrate that an algorithm based on PTT and HRV spectral analysis is able to classify and distinguish sleep stages with high accuracy and sensitivity. In addition the proposed algorithm is capable to be improved and implemented as a wearable, comfortable and cheap instrument for sleep screening.